The T cell antigen receptor (TCR) was shown to be a clone specific disulfide-linked heterodimer on T cells, composed of two glycosylated subunits, one of which is designated the .alpha. chain and the other of which is designated the .beta. chain. The .alpha. and .gamma.TCR subunits have a relative molecular mass (M.sub.r) of approximately 50,000 and 40,000 daltons, respectively (Allison et al., 1982, Immunol. 129:2293-2300; Meuer et al., 1983, J. Exp. Med. 157:705-719; Haskins et al., 1983, J. Exp. Med. 157:1149-1169). Genes that rearrange during T cell ontogeny and encode the .gamma.TCR (Yanagi et al., 1984, Nature 308:145-149; Hedrick et al., 1984, Nature 308:153-158) and .gamma.TCR (Chien et al., 1984, Nature 312:31-35; Saito et al., 1984, Nature 312:36-40, Sim et al., 1984, Nature 312:771-775) subunits were isolated either by subtractive hybridization or by probing with oligonucleotides.
The alpha and beta chains of the T cell antigen receptor of a T cell clone are each composed of a unique combination of domains designated variable (V), diversity (D), joining (J), and constant (C) (Siu et al., 1984, Cell 37:393; Yanagi et al., 1985, Proc. Natl. Acad. Sci. USA 82:3430). Hypervariable regions have been identified (Patten et al., 1984, Nature 312:40; Becker et al., 1985, Nature 317:430). In each T cell clone, the combination of V, D and J domains of both the alpha and the beta chains participates in antigen recognition in a manner which is uniquely characteristic of that T cell clone and defines a unique binding site, also known as the idiotype of the T cell lone. In contrast, the C domain does not participate in antigen binding.
A unique feature of the human .alpha.,.beta.TCR was the observed comodulation (Meuer et al., 1983, J. Exp. Med. 157:705-719), coimmunoprecipitation (Oettgen, et al., 1984, J. Biol. Chem. 259:12,039-12,048), and required coexpression (Weiss et al., 1984, J. Exp. Med. 160:1284-1299) of the .alpha.,.beta.TCR molecules with a CD3 glycoprotein complex. Subsequently, the direct physical association of the two protein complexes was demonstrated by chemically cross-linking the .alpha.,.beta.TCR molecules to the T3 glycoprotein and identifying the components of the cross-linked complex as the TCR subunit and the T3 glycoprotein (M.sub.r 28,000) subunit (Brenner et al., 1985, Cell 40:183-190). A T3 counterpart is similarly associated with murine .alpha.,.beta.TCR (Allison et al., 1985, Nature 314:107-109; Samelson et al., 1984, Immunol. Rev. 81:131-144).
A third gene that rearranges in T cells, designated .gamma.TCR, was identified, first in mice (Saito et al, 1984, Nature 309:757-762; Kranz et al., 1985, Nature 313:762-755; Hayday et al., 1985, Cell 40:259-269) and then in humans (Lefranc et al., 1985, Nature 316:464-466; Murre et al., 1985, Nature 316:549-552). The human .gamma.TCR locus appears to consist of between five and ten variable, five joining, and two constant region genes (Dialynas et al., 1986, Proc. Natl. Acad. Sci. U.S.A. 83: 2619). Although the total number of functional variable and joining regions is limited, significant diversity is introduced during the process of V-J joining (Kranz et al., 1985, Nature 313:752-755; Lefranc et al., 1986, Cell 45:237-246; Quertermaus et al., 1986, Nature 322:184). The .gamma.TCR gene rearrangements occur in lymphocytes with suppressor-cytotoxic as well as helper phenotypes (Lefranc et al., 1985, Nature 316:464-466; Murre et al., 1985, Nature 316:549-552, Quertermaus et al., 1986, Science 231:252-255; Lefranc et al., 1986, Cell 45:237-246, Iwamoto et al., 1986, J. Exp. Med. 163:1203-1212; Zauderer et al., 1986, J. Exp. Med. 163:1314-1318).
During T cell ontogeny, it has been shown that .gamma.TCR gene rearrangement precedes .beta. and .alpha.TCR gene rearrangement (Roulet et al., 1985, Nature 314:103-107; Snodgrass et al., 1985, Nature 315:232-233).